Hormone Therapy Or Chemotherapy Before Surgery Based on Gene Expression Analysis in Treating Patients With Breast Cancer

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This randomized pilot clinical trial studied whether the Oncotype DX gene expression "Recurrence Score" (RS) would be useful for helping make a decision about which type of pre-operative treatment, hormone therapy or chemotherapy would be a better for patients with hormone responsive cancers that were not suitable for breast conserving surgery. The RS is currently used to predict the risk of distant recurrence and the benefit of the addition of chemotherapy to hormonal therapy in the adjuvant setting.

Assessed the feasibility of carrying out a large-scale multi-center trial in which recurrence score (RS) was used to select treatment type in the neoadjuvant setting. Whether patients with intermediate RS were willing to be randomized between hormonal and chemotherapy.

The treatment received was not experimental and considered standard treatment for the type of cancer the participants had. What was experimental included the way in which they were assigned to a type of treatment. The design of this study was used to help determine if RS can be used to predict which type of treatment women with breast cancer are most likely to benefit from.

OUTLINE: Patients are assigned to 1 of 3 groups based on RS following Oncotype Dx gene expression profiling.

Patients with a Recurrence Score (RS) less than 11 (RS <11) are assigned to Group 1, neoadjuvant hormonal therapy either tamoxifen (pre-menopausal women) or an aromatase inhibitor (post-menopausal women) for 4-6 months in the absence of disease progression or unacceptable toxicity.

Undergo Oncotype Dx gene expression profiling. The Oncotype DX gene expression profiling system will be used to calculate a "Recurrence Score" (RS).

Drug: Tamoxifen Citrate

Undergo hormonal therapy

Other Names:

Nolvadex

TAM

tamoxifen

TMX

hormonal therapy

Drug: Aromatase Inhibition Therapy

Undergo hormonal therapy

Other Names:

Inhibition therapy, aromatase

Aromatase Inhibition

hormonal therapy

Experimental: Group 2 Arm 2 (RS 11-25)

Patients with an intermediate RS(11-25) assigned to Group 2. Randomized to Arm 2, neoadjuvant chemotherapy 6-8 courses of anthracycline/taxane based regimen over 4-6 months in the absence of disease progression or unacceptable toxicity.

Treatment:

Neoadjuvant therapy

Therapeutic conventional surgery

Laboratory biomarker analysis/Correlative studies

Gene Expression Analysis/Oncotype DX Gene Expression Profiling System

Systemic chemotherapy

Procedure: Neoadjuvant Therapy

Undergo neoadjuvant therapy

Other Names:

Induction Therapy

Neoadjuvant

Preoperative Therapy

Procedure: Therapeutic Conventional Surgery

Undergo therapeutic conventional surgery

Other: Laboratory Biomarker Analysis

Correlative studies

Other Name: Correlative studies

Genetic: Gene Expression Analysis

Undergo Oncotype Dx gene expression profiling. The Oncotype DX gene expression profiling system will be used to calculate a "Recurrence Score" (RS).

Drug: Systemic Chemotherapy

Undergo chemotherapy

Experimental: Group 3 (RS > 25)

Patients with a high RS (> 25) assigned to Group 3, neoadjuvant chemotherapy as in Group 2 Arm 2.

Treatment:

Neoadjuvant therapy

Therapeutic conventional surgery

Laboratory biomarker analysis/Correlative studies

Gene Expression Analysis/Oncotype DX Gene Expression Profiling System

Systemic chemotherapy

Procedure: Neoadjuvant Therapy

Undergo neoadjuvant therapy

Other Names:

Induction Therapy

Neoadjuvant

Preoperative Therapy

Procedure: Therapeutic Conventional Surgery

Undergo therapeutic conventional surgery

Other: Laboratory Biomarker Analysis

Correlative studies

Other Name: Correlative studies

Genetic: Gene Expression Analysis

Undergo Oncotype Dx gene expression profiling. The Oncotype DX gene expression profiling system will be used to calculate a "Recurrence Score" (RS).

The Proportion of Patients With RS 11-25 Who Refused the Assigned Treatment [ Time Frame: Up to 2 years ]

The primary purpose of this trial is to determine the feasibility of carrying out a large multi-center trial with a similar design. Feasibility, in terms of less than 1/3 of patients with intermediate (11-25) Recurrence Score (RS) who refused the assigned treatment (Group 2) or refused randomization between hormonal (Arm 1) or chemotherapy (Arm 2). The confidence interval will be 95%. The proportion (and 95% confidence interval) of patients with RS 11-25 who refuse the assigned treatment will be calculated.

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Ages Eligible for Study:

18 Years and older (Adult, Senior)

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

The treating surgeon must determine that breast conservation therapy (BCT) would be made more feasible by reducing tumor size using neoadjuvant systemic therapy

The patient must have signed and dated an institutional review board (IRB) approved consent form that conforms to federal and institutional guidelines

The patient must be female

The patient must be greater than or equal to 18 years old

The patient must have an Eastern Cooperative Oncology Group Score (ECOG) performance status of 0 or 1

The diagnosis of invasive carcinoma of the breast must have been made by core needle biopsy

The primary breast tumor must be >= 2 cm by physical exam or imaging

Ipsilateral axillary lymph nodes must be evaluated by imaging (MRI or ultrasound) within 6 weeks prior to randomization; If indicated for abnormal lymph nodes, fine needle aspirate (FNA) or core biopsy must be performed.

The tumor must have been determined to be HER2-negative as follows:

Fluorescent in situ hybridization (FISH)-negative (defined by ratio of HER2 to Chromosome 17 centromere (CEP17) must be < 2.2) or, if a ratio was not performed, the HER2 gene copy number must be < 4 per nucleus; or

Chromogenic in situ hybridization (CISH) is performed, the result must indicate a HER2 gene copy number of < 6 per nucleus; or

Immunohistochemistry (IHC) 0-1+; or

IHC 2+ and FISH-negative or CISH-negative

The tumor must have been determined to be ER+ and/or progesterone positive (PgR+) defined as > 10% tumor staining by immunohistochemistry

The patient must have been evaluated by a treating physician, reviewed and discussed by the multi-disciplinary breast team, and considered to be a candidate for chemotherapy

Ipsilateral cN2b or cN3 disease (patients with cN1 or cN2a disease are eligible)

Definitive clinical or radiologic evidence of metastatic disease (Note: chest imaging [mandatory for all patients] and other imaging [if required] must have been performed within 6 weeks prior to randomization)